Plasma Gel Could Be Used to Deliver PTH-producing Cells to Treat Hypoparathyroidism, Study Shows

A plasma gel scaffold, easily injected and capable of delivering cells that produce and release the parathyroid hormone (PTH), could be a potential new treatment for hypoparathyroidism patients, a study reports.

The study, “Feasibility of autologous plasma gel for tonsil-derived stem cell therapeutics in hypoparathyroidism,” was conducted by Korean researchers and published in Scientific Reports.

Hypoparathyroidism is caused by low levels of PTH in the body. Conventional treatments, including vitamin D and calcium supplements, fail to completely mimic the effects of PTH in the body and can cause discomfort to patients because of their side effects.

More recently, Natpara — a synthetic form of PTH that can be injected in the body — was approved by the U.S. Food and Drug Administration for the treatment of osteoporosis and hypoparathyroidism. While it is able to deliver PTH and simulate its effects, the therapy doesn’t last long in the body, requiring daily injections to be effective. In addition, it is still an expensive treatment option.

An option to bypass the short-term effects of Natpara could be the transplantation of engineered tissue that constantly releases PTH. To do this, researchers need a suitable material in which to deliver cells, called a scaffold, which acts like a template for cells to grow in. So far, different types of scaffold materials for this purpose have been tested and discarded due to several technical limitations.

Plasma gel (PG) is a biologic gel derived from blood that has several advantages over other types of scaffold materials, including posing less risk of infection or rejection, providing excellent conditions for cell culture, and being easy to manipulate.

Researchers tested the feasibility of using plasma gel as a scaffold material to deliver tonsil-derived mesenchymal stem cells (TMSCs) — stem cells derived from the tonsils — grown into cells that produce PTH as a treatment for hypoparathyroidism.

To do this, they first isolated plasma from rat blood and fabricated plasma gel using a special heating machine. They then surgically removed the parathyroid gland from five groups of animals (PTX groups) to mimic hypoparathyroidism, and performed a sham operation, or placebo surgery, in another group used as controls.

Each PTX group received either normal TSMCs alone (cTMSC); TSMCs together with plasma gel (cTMSC-PG);  TSMCs differentiated into parathyroid cells alone (dTMSC); or dTMSCs together with plasma gel (dTMSC-PG). These cells were administered by an injection into the muscle of the animal’s dorsum. One PTX group received only plasma gel.

Intact PTH was detected 21 days after injection in the groups that received the plasma gel (cTMSC-PG and dTMSC-PG groups) but not in groups transplanted with TMSCs only (cTMSC and dTMSC groups), or with plasma gel only.

“These results indicated that intact PTH levels were restored only in the groups for which we used the plasma gel as the cell-delivery scaffold,” the authors wrote.

After examining the cTMSC-transplanted regions at the animal’s dorsum, researchers observed PTH and chromogranin A were both being expressed by cells. Chromogranin A induces and promotes the generation of secretory granules, and gives rise to small proteins that regulate the interactions between the nervous system and the endocrine system of certain cells.

These findings suggest that plasma gel is a solid scaffold material to deliver cells that produce and release PTH and could be considered as a potential treatment for hypoparathyroidism.

“The study results indicate that PG is human-applicable, easily injectable, and cell-friendly material. Administration of PTH-secreting tonsil-derived stem cells with plasma gel is a highly feasible treatment modality for treating hypoparathyroidism patients,” the authors concluded.